Is ABCA12 p.Phe2201Ser (c.6602T>C) pathogenic?

ABCA12 p.Phe2201Ser (c.6602T>C) is classified Uncertain significance in ABCA12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-31). AlphaMissense: likely pathogenic (0.9349); Very rare (popmax 0.0011%, sas).

How common is ABCA12 p.Phe2201Ser (c.6602T>C) in the general population?

ABCA12 p.Phe2201Ser (c.6602T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ABCA12 p.Phe2201Ser (c.6602T>C)?

AlphaMissense predicts likely pathogenic (score 0.9349) — an in-silico prediction, not a clinical call.

ABCA12 p.Phe2201Ser

c.6602T>C · VCV3383898

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9349	likely pathogenic
REVEL	0.888	moderately pathogenic-leaning
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 85 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 6.2e-05% 1/1,614,034 alleles · very rare exomes 1/1,461,756 · genomes 0/152,278 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCA12
Protein: p.Phe2201Ser
Coding: c.6602T>C
MANE Select: NM_173076
Type: single nucleotide variant
Location: chr2:214953899 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 2201: a UniProt-annotated variant site (in arci4b); a UniProt-annotated variant site (in arci4b; uncertain significance)

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 p.Phe2201Ile Likely benign ★★ ⚠ same residue
ABCA12 c.2592+1G>A Likely pathogenic ★★ same type
ABCA12 c.5381+1G>C Pathogenic/Likely pathogenic ★★ same type
ABCA12 c.985+1G>A Likely pathogenic ★★ same type
ABCA12 p.Arg1297Ter Pathogenic ★★ same type
ABCA12 p.Arg1514Cys Pathogenic ★★ same type
ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Arg1515Ter Pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abca12-p-phe2201ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown